Most of us have somewhere around a trillion tiny platelets zooming around our bloodstreams. Joseph Italiano, PhD, of Boston Children’s Hospital’s Vascular Biology Program, calls them the “Swiss Army knives of the blood.” In addition to their key role in clotting, platelets are important in immunity, wound healing, chemical delivery, blood vessel development and more.

At healthcare facilities, platelets are in constant demand for patients with blood diseases, or those receiving radiation or chemotherapy for cancer. But unlike other blood products, platelets can’t be stored for more than a few days. If there’s a snowstorm or other emergency preventing donors from giving platelets, a hospital can easily run out. So researchers have been trying to make platelets in a lab setting.

Two teams at Boston Children’s Hospital are tackling the problem in slightly different ways. …

Ed. note: This is an update of a post that originally appeared in 2014.

The neural tube is supposed to close during the first month of prenatal development, forming the spinal cord and the brain. In children with spina bifida, it doesn’t close completely, leaving the nerves of the spinal cord exposed and subject to damage. The most common and serious form of spina bifida, myelomeningocele, sets a child up for lifelong disability, causing complications such as hydrocephalus, leg paralysis, and loss of bladder and bowel control.

A growing body of research from Boston Children’s Hospital, though still in animal models, suggests that spina bifida could be repaired at least partially early in pregnancy, through intrauterine injections of a baby’s own cells. …

Scientists studying how genetics impact brain disease have long sought a better experimental model. Cultures of genetically-modified cell lines can reveal some clues to how certain genes influence the development of psychiatric disorders and brain cancers. But such models cannot offer the true-to-form look at brain function that can be provided by genetically-modified mice.

Even then, carefully breeding mice to study how genes impact the brain has several drawbacks. The breeding cycles are lengthy and costly, and the desired gene specificity can only be verified — but not guaranteed — when mouse pups are born.

In today’s Nature, scientists from Boston Children’s Hospital and UC San Francisco describe a new way to create customized mouse models for studying the brain. …

Nucleoli, the structures in the cell nucleus that manufacture ribosomes, are enlarged in very early brain development, indicating an increase in ribosome production. Here, a 3D reconstruction of individual nucleoli. (Kevin Chau, Boston Children’s Hospital)

In our early days as embryos, before we had brains, we had a neural fold, bathed in amniotic fluid. Sometime in the early-to-mid first trimester, the fold closed to form a tube, capturing some of the fluid inside as cerebrospinal fluid. Only then did our brains begin to form.

In 2015, a team led by Maria Lehtinen, PhD, Kevin Chau, PhD and Hanno Steen, PhD, at Boston Children’s Hospital, showed that the profile of proteins in the fluid changes during this time. They further showed that these proteins “talk” to the neural stem cells that form the brain.

Amniotic fluid is routinely withdrawn for prenatal testing. It could also be a delivery route for fetal cell therapy to treat congenital anomalies, with broader applications than once thought.

The amniotic fluid surrounding babies in the womb contains fetal mesenchymal stem cells (MSCs) that can differentiate into many cell types and tissues. More than a decade ago, Dario Fauza, MD, PhD, a surgeon and researcher at Boston Children’s Hospital, proposed using these cells therapeutically. His lab has been exploring these cells’ healing properties ever since.

Replicated in great quantity in the lab and then reinfused into the amniotic fluid in animal models — a reverse amniocentesis if you will — MSCs derived from amniotic fluid have been shown to repair or mitigate congenital defects before birth. In spina bifida, they have induced skin to grow over the exposed spinal cord; in gastroschisis, they have reduced damage to the exposed bowel. Fauza calls this approach Trans-Amniotic Stem Cell Therapy, or TRASCET.

The yellow-green cells in this “mini-stomach” are capable of making insulin. The mini-organ was made from biopsied cells from mouse stomachs, with reprogramming factors added.

If only there were a cure. David Breault, MD, PhD, associate chief of the Division of Endocrinology at Boston Children’s Hospital, was seeing patient after patient with Type I diabetes. Children facing lifetimes of insulin injections, special diets and the threat of long-term complications including blindness, heart disease and kidney failure.

Breault knew that patients with type I diabetes mysteriously destroy their own insulin-producing beta cells. He had read reports of researchers transplanting beta cells to supplement insulin. These transplants, even when successful, required powerful immunosuppressant medications to prevent patients’ immune systems from attacking the donor cells.

But Breault was also aware that investigators had, for a decade, been looking to stem cells as the source of a constantly renewing supply of beta cells. Advancing that promise, he has now found a way to convert patients’ own cells — from the stomach and intestine — into beta cells that produce insulin. …

Although Gianna was treated surgically, Dario Fauza, MD, hopes to someday use stem cells from the amniotic fluid, multiplied and returned to the womb, to naturally heal gastroschisis and other birth defects. (Courtesy Danielle DeCarlo)

Except when spreading awareness about her condition, 6-year-old Gianna DeCarlo prefers not to wear two-piece bathing suits because of the long vertical scar on her stomach. “Even though nobody’s said anything, she feels like she’ll be made fun of,” says her mother, Danielle. “I do what I can to make her love her body.”

Gianna doesn’t remember her three surgeries or the nasogastric tube she needed as an infant, before she was able to eat normally. She was born with gastroschisis, a striking birth defect in which the abdominal wall doesn’t seal fully during fetal development. As a result, her intestines developed outside her body. She was fed through an IV for several weeks, and was finally stitched fully shut at age 2. …

Could regenerative techniques restore hearing or balance by replacing lost sensory cells in the inner ear? Lab-created inner-ear organs, described today in Nature Communications, could provide helpful three-dimensional models for testing potential therapies.

The lab-built sac-like structure above, about 1 millimeter in size, contains fully-formed balance organs resembling the utricle and saccule, which sense head orientation and movement and send impulses to the brain. The tiny organs were built from mouse embryonic stem cells in a 3-D tissue culture in work led by Jeffrey Holt, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and Eri Hashino, PhD, of the University of Indiana. …

Blood-brain barrier on chip

(Wyss Institute at Harvard University)

The blood-brain barrier protects the brain against potentially damaging molecules, but its gate-keeping can also prevent helpful drugs from getting into the central nervous system. Reporting in PLoS One, a team at the Wyss Institute for Biologically Inspired Engineering describes a 3-D blood-brain barrier on a chip — a hollow blood vessel lined with living human endothelial cells and surrounded by a collagen matrix bearing human pericytes and astrocytes. …

It’s long been a mystery why some of our cells can have mutations associated with cancer, yet are not truly cancerous. Now researchers have, for the first time, watched a cancer spread from a single cell in a live animal, and found a critical step that turns a merely cancer-prone cell into a malignant one.

Their work, published today in Science, offers up a new set of therapeutic targets and could even help revive a theory first floated in the 1950s known as “field cancerization.”

“We found that the beginning of cancer occurs after activation of an oncogene or loss of a tumor suppressor, and involves a change that takes a single cell back to a stem cell state,” says Charles Kaufman, MD, PhD, a postdoctoral fellow in the Zon Laboratory at Boston Children’s Hospital and the paper’s first author. …